Immunologic approaches to cancer therapy are based on the notion that cancer cells have somehow evaded the body's defenses against aberrant or foreign cells and molecules, and that these defenses might be therapeutically stimulated to regain the lost ground, see e.g., pp. 623-648 in Klein (1982) Immunology, Wiley-Interscience, New York. The recent observations that various immune effectors can directly or indirectly inhibit tumor growth has led to renewed interest in this approach to cancer therapy, see e.g., Herberman (1985) Concepts Immunopathol. 1:96-132 (1985) (natural killer cells resist tumor cell growth); Rosenberg, et al. (1988) Ann. Rev. Immunol. 4:681-709 (clinical use of IL-2-activated killer cells to treat cancer); Ralph, et al. (1988) J. Exp. Med. 167:712-717 (tumoricidal activity by macrophages stimulated by lymphokines); Tepper, et al. (1989) Cell 57:503-512 (IL-4 has anti-tumor activity); M. Cohen, "Lymphokines and Tumor Immunity," pp. 237-253 in S. Cohen (ed.) (1990) Lymphokines and the Immune Response, CRC Press, Boca Raton; and the like.
For example, leukemias are a heterogeneous group of neoplasms arising from the malignant transformation of hematopoietic cells, and can be derived from either lymphoid or myeloid cell types. The transformed cells proliferate primarily in the bone marrow and lymphoid tissue where they interfere with normal hematopoiesis and immunity. They may also emigrate into the blood and infiltrate other tissues often leading to abnormal distributions of different cell types. Examples of leukemias include, acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), hairy cell leukemia, and adult T cell leukemia (ATL).
Leukemias are typically identified as either acute or chronic. Acute forms have a rapid clinical course and without effective treatment can result in death within months. Acute leukemias are typically characterized by excessive proliferation of immature myeloid or lymphoid cells in the bone marrow, as a result of defects in the maturation process. In AML, the cells fail to mature beyond the myeloblast or promyelocyte level. In ALL, the cells fail to mature beyond the lymphoblastoid level.
Chronic leukemias have a more prolonged natural history. CLL is typically characterized by the overproduction and accumulation of mature appearing B lymphocytes. The neoplastic cells usually have B cell associated markers such as monoclonal surface IgM and Fc receptors. Approximately 5 percent of patients with CLL have the T cell form of CLL. The neoplastic cells in these diseases form rosettes with sheep erythrocytes and exhibit other T cell markers.
Hairy cell leukemia is a lymphoid neoplasm characterized by neoplastic cells having cytoplasmic projections. The disease is caused by the expansion of mature B cells which often produce monoclonal immunoglobulins.
Adult T cell leukemia (ATL) is associated with human T cell leukemia virus-I (HTLV-I). It is an aggressive malignancy of mature T cells, and is endemic to parts of Japan, the Caribbean, and Africa.
Lymphomas, in contrast to leukemias, are neoplastic transformations of cells that reside predominantly in lymphoid tissues. Lymphomas are typically divided between Hodgkin's disease and non-Hodgkin's lymphomas. In Hodgkin's disease the majority of the cells are small lymphocytes with a T cell phenotype. More than 90% of all cases of non-Hodgkin's lymphomas are of B cell derivation.
Treatment of the majority of these diseases has not been entirely successful. Prior art approaches have centered primarily on chemotherapy and radiation. To date, however, these treatments generally fail to effect long term remission or cure. Thus, the prior art lacks a safe, reliable treatment of neoplastic cell proliferation, particularly those which are IL-2-dependent. Recently, various models have provided data which support use of IL-10 to treat neoplastic conditions.